Bcl‐2 overexpression prevents apoptosis induced by ceramidase inhibitors in malignant melanoma and HaCaT keratinocytes

FEBS Letters

Goltz, Gerit¹  Eberle, Jürgen¹  Bielawska, Alicja²  Raisova, Monika¹  Hannun, Yusuf A²  Riebeling, Christian¹  Orfanos, Constantin E¹  Hossini, Amir M¹  Bektas, Meryem¹  Geilen, Christoph C¹ 

[1] Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, 14195 Berlin, Germany;Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA

关键词: Ceramide;    Ceramidase;    Melanoma;    HaCaT keratinocyte;    Bcl-2;    D-e-MAPP;    (1S;    2R)-2-N-myristoylamino-1-phenyl-1-propanol;    L-e-MAPP;    (1R;    2S)-2-N-myristoylamino-1-phenyl-1-propanol;    D-NMAPPD;    (1R;    2R)-2-N-myristoylamino-1-(4-nitrophenyl)-1;    3-propandiol;    C2-ceramide;    (2S;    3R)-N-acetylsphingosine;    LDH;    lactate dehydrogenase;   

DOI  :  10.1016/S0014-5793(02)02472-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We examined the biological effects of the ceramide analogues (1S,2R)-2-N-myristoylamino-1-phenyl-1-propanol (D-e-MAPP) and (1R,2R)-2-N-myristoylamino-1-(4-nitrophenyl)-1,3-propandiol (D-NMAPPD) on human HaCaT keratinocytes and human melanoma cells. We could demonstrate that D-e-MAPP and D-NMAPPD are able to suppress acid ceramidase activity. The elevation of the endogenous level of ceramide is followed by induction of apoptosis and suppression of proliferation in HaCaT keratinocytes. Moreover, we recently identified a group of human melanoma cell populations which are heterogeneously susceptible to C₂-ceramide-mediated apoptosis. Studies with these melanoma cells revealed correlation between ceramide-mediated apoptosis and D-NMAPPD-induced apoptosis, confirming the effect of this inhibitor on ceramide signaling in human melanoma cells. These findings suggest ceramidase inhibitors as a potential new therapeutical class of antiproliferative and cytostatic drugs.

【 授权许可】

Unknown